Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...

Metformin, a biguanide, is a widely used anti-diabetic drug which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible towards oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and D Galactose induced rat model) were supplemented with metformin (300 mg/kg b...

An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system...

BACKGROUND: Diabetic patients with heart failure (HF) treated with insulin appear to have a worse prognosis compared to oral anti-diabetic (OAD) agents. Whether insulin is a risk factor or a marker of disease severity is unknown. We studied the prognostic impact of insulin treatment in an acute HF diabetic population. METHODS: From a prospectively recruited population of hospital-admitted acute HF patients we retrospectively selected a convenience sample. Pair-matched analysis: each insulin-treated patient was matched with a diabetic patient with similar glycated haemoglobin (HbA1c±0...

Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer, however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden (PCBaSe) 3.0, with data on T2DM, use of metformin, sulphonylurea, and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders...

BACKGROUND AND AIM: The number of patients with type 2 diabetes (T2DM) is increasing. Most patients with T2DM are uncontrolled and fail to achieve their target Hba1c. In recent years, newer agents such as SGLT2 inhibitors (SGLT2i) have been approved for clinical use. Though data from clinical trials and sub set analysis of Indian patients in global studies are promising, real world evidence from standard clinical practice in India is lacking. The aim of this study was to analyze the metabolic parameters in patients with T2DM on SGLT2i in real world clinical practice...

The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome...

OBJECTIVE: Rational prescribing in older people is a priority for health care organizations. The STOPP/START screening tool has been developed to identify potentially inappropriate prescribing (PIP) in individuals. In a primary care setting, STOPP/START can estimate PIP prevalence and related factors at population level. The aim of this study is to measure the prevalence rates of PPI in elderly population using clinical and prescription claim databases. DESIGN: Cross-sectional population study...

Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer...

PURPOSE: The purpose of this study is to characterise how Type 2 Diabetes Mellitus (T2DM) is treated in England and Wales and whether this adheres to 2009 National Institute for Health and Care Excellence (NICE) guidance on management of T2DM. METHODS: Data for T2DM patients aged 18+ years prescribed at least one anti-diabetic drug between 01/01/2000-30/06/2012 were extracted from the Clinical Practice Research Datalink. We examined the sequences in which anti-diabetic drugs were prescribed and, for patients on the most common anti-diabetic drug pathways, evaluated average HbA1c values at treatment initiation and at progression to a second or third-line anti-diabetic drug class, including insulin...

OBJECTIVES: This study aimed to investigate the effect of metformin on survival of people with type 2 diabetes and pleural mesothelioma. MATERIALS AND METHODS: We conducted a retrospective cohort study of people with type 2 diabetes diagnosed with pleural or unspecified mesothelioma between 1993 and 2014 using linked Scottish population-based diabetes and cancer datasets. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards regression models were used to describe the association between use of metformin and all-cause mortality following diagnosis of pleural mesothelioma...

Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected...

PURPOSE: To estimate the incidence of lactic acidosis (LA) and role of metformin in Japanese patients with type 2 diabetes mellitus (T2DM) treated with anti-diabetes drugs. METHODS: This retrospective propensity score matched cohort study was conducted using the Japanese Medical Data Vision claims database. T2DM patients aged 18 or above who received diabetes drugs during January 2010 through August 2014 were identified. Cases of LA were identified based on reimbursement codes and confirmed by lactic acid test and subsequent treatment by hemodialysis or intravenous sodium bicarbonate...

AIMS: Subclinical hypercortisolism was reported to be more prevalent among diabetic, obese and hypertensive patients. Our primary aim was to investigate the prevalence of subclinical hypercortisolism in patients from the Rio de Janeiro Type 2 Diabetes (RIO-T2D) Cohort; and secondarily to assess its associated factors. METHODS: From May 2013 to August 2014, 393 diabetic outpatients underwent overnight 1mg dexamethasone suppression test (DST). Patients with non-suppressive morning cortisol (≥1...

Metformin, a biguanide drug commonly used to treat type 2 diabetes, has been noted to function as a caloric restriction mimetic. Its antidiabetic effect notwithstanding, metformin is currently being considered an antiaging drug candidate, although the molecular mechanisms have not yet been unequivocally established. This study aims to examine whether short-term metformin treatment can provide protective effects against oxidative stress in young and old-age rats. Young (age 4 months) and old (age 24 months) male Wistar rats were treated with metformin (300 mg/kg b...

BACKGROUND: The aim of this study was to examine the association between glycemic excursions before treatment and glycosylated hemoglobin (HbA1c) reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). METHODS: T2D patients on mono- or dual- oral anti-diabetes drugs with HbA1c of 7.0 ~ 11.0 % (53 ~ 97 mmol/mol) were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide as add-on treatment for 16 weeks...

INTRODUCTION: Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. AIM: To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone...

BACKGROUND AND AIMS: Endothelial dysfunction, vascular inflammation and oxidative stress have been integrally linked to the pathogenesis of both type 2 diabetes and cardiovascular disease. Aged Garlic Extract (AGE), a potent antioxidant, has been shown in previous studies to attenuate these novel risk factors in a non-diabetic population. AIMS: This study tested the hypothesis that AGE may improve endothelial function, oxidative stress, vascular inflammation and insulin resistance in high risk cardiovascular subjects with type 2 diabetes...